Determining one or more analyte concentrations in a bodily fluid may be performed by photometric/optical measurements. In this manner, a body fluid sample may be applied onto a test carrier, which then is illuminated by light to perform the photometric measurement. Typically, reflective measurements are performed to determine an amount of light elastically or inelastically reflected, scattered, or remitted by the test carrier. In general, such a test carrier uses at least one test chemical (i.e., one or more chemical compounds or chemical mixtures) adapted for performing a detectable reaction, which leads to a detectable change of the test carrier such as, for example, an optical change, especially a color change. The test chemical also may be referred to as a test substance, a test chemistry, a test reagent, a detection reagent, or a detector substance. For details of potential test chemicals and test carriers incorporating such test chemicals, which may be used within the context of the present disclosure, reference is made to Hönes et al. (2008) Diabetes Technol. Ther. 10:S10-S26. Other types of test chemicals, test substances and/or test carriers are feasible and may be used in connection with the present disclosure.
By using one or more test chemicals, the detection reaction may be initiated, the course of which depends on the analyte concentration to be determined. Typically, the test chemical is adapted to perform at least one detection reaction when the analyte is present in the body fluid sample, where the extent and/or degree of the detection reaction, such as the kinetics of the detection reaction, depends on the analyte concentration. In case of photometric measurements, the test carrier may be illuminated with light, where the light may be diffusely reflected from the test carrier and detected by an analyzing device. For example, the analyte concentration in a body fluid sample can be determined by measuring the reflectivity of the test carrier when the detection reaction is completed. Additionally or alternatively, the progress of the detection reaction may be monitored by measuring a temporal change of the reflectivity. Thus, in photometric measurements, the test chemical may be adapted to change at least one reflective property (i.e., a color) due to the detection reaction.
Measuring and analyzing remitted light typically imposes some technical challenges. On the one hand, these measurements can involve small currents and/or voltages. Measuring such small currents or voltage, however, is challenging since interferences may occur such as, for example, interferences due to low-frequency voltages. On the other hand, optical disturbances may occur because of ambient light. Thus, when determining the analyte concentration with photometric measurements, analyzing devices and methods are needed that reduce inference of these disturbances.
EP Patent No. 0 632 262 discloses methods of detecting and evaluating analog photometric signals in a test carrier analysis apparatus. The test field of the test carrier is irradiated by a light source that is clocked in light and dark phases. The light and dark phases form an irregular sequence with a frequency spectrum having a large number of different frequencies. The light is reflected and detected by a measurement receiver, and its measured value is passed to a measurement integrating and digitalizing circuit for evaluation, where the irregular signal is filtered out.
Likewise, EP Patent No. 1 912 058 discloses systems adapted for measuring and evaluating optical signals for detecting an analyte in an analysis liquid. The system includes a test carrier and a light source for illuminating an optical evaluation zone of the test carrier. In addition, the systems include two signal sources adapted for generating two control signals, mixed by a mixer unit to generate a light control signal for the light source. A light sensor receives the remitted light and converts it into a measuring signal. Further, the systems include two frequency-selective amplifiers, each receiving the measurement signal and one of the control signals, and an evaluation unit to which the output signal of the frequency-selective amplifiers are fed. In the evaluation unit, the output signals are compared, and information about interference of the measurement by external light is determined from the result of the comparison. When an interference of the measurement is above a certain threshold, the measurement is recognized as faulty and is rejected. Thus, no analyte concentration is provided.
Further, and in many cases, the test carrier must be oriented within the device for determining one or more analyte concentrations such that the device is able to perform the test. For example, US Patent Application Publication No. 2003/0169426 discloses test meters capable of determining the orientation of a test carrier within it. The test carrier has a first major surface and an opposing second major surface. Each major surface includes an orientation indicator region, where the orientation indicator regions differ by at least one optical property such as, for example, reflectance. The test meter includes a test region for accepting a test carrier and also includes an optical orientation sensor. The optical orientation sensor generates an orientation signal indicative of an optical property of the orientation indicator region.
Likewise, U.S. Pat. No. 5,526,120 discloses test carriers and apparatuses where each has an asymmetry. The asymmetries combine to permit a test carrier to be inserted into the apparatus when it is correctly aligned but prevent the test carrier from being fully inserted if it is wrong side up. In addition, the apparatus can detect whether or not the test carrier has been fully inserted.
Despite the advantages implied by the known devices and methods, many technical challenges remain. For example, many known devices and methods are not suited for recognizing disturbances—both internal and external—before or while measuring. For example, internal disturbances have to be considered, such as fluctuations of one or more light sources and/or noise within electronic components of the devices. Further, external disturbances have to be considered, such as disturbances induced by ambient light. Such disturbances may lead to significant faults and falsifications of the measured analyte concentrations.
Known devices and methods, however, allow for fault detecting only at the end of each measurement. For example, paragraph [0047] of EP Patent No. 1 912 058 discloses comparing analytical results that have been determined from raw data of output signals of a frequency-selective amplifier, and not raw data directly. Thus, in case a measurement is rejected, the whole test carrier wetted by the sample is rejected, and a new sample has to be applied on a new test carrier, implying that the new sample has to be taken from a patient or user. Thus, many known devices and methods typically imply a drawback that test carriers are wasted and that the user or patient, at least to some extent, will have to generate repeated body fluid sample to obtain a reliable measurement. Further, and in view of an increased use of modern light sources like energy-saving lamps, light-emitting diodes (LEDs), etc., and in view of an increased trend towards miniaturization of analytical devices, disturbances of photometric measurements may increase. Consequently, a strong need exists for devices and methods that are suited to at least partially avoid waste of test carriers and frequent generation of samples yet still provide fast and reliable measurement results.
Further, EP Patent No. 1 912 058 discloses that a first signal source generates a first control signal with a base frequency and a second signal source generates a second control signal with a frequency that is a multiple of the base frequency. The intensities of the first control signal and the second control signal are different from each other. However, using control signals with different intensities may enhance the possibility of faulty fault detecting in case of low measurement signals because of faultily identifying a low measurement signal and not detecting a disturbance. Thus, even though a valid measurement signal was measured, the valid measurement signal may erroneously be identified as a disturbance rather than as a valid measurement signal.
It is therefore an object of the present disclosure to provide methods and devices for determining an analyte concentration in a body fluid sample that overcome the above-mentioned drawbacks. Moreover, the methods and devices disclosed herein are capable of reliably determining an analyte concentration in a body fluid even in the presence of disturbances.